Without limiting the scope of the invention, its background is described in connection with the use of tetrahydrobiopterin (BH4) in Fabry disease as: (i) a novel biomarker for diagnosis and of the severity of the disease, (ii) as a marker to follow the metabolic correction of the various therapies, and (iii) as a replacement therapy for Fabry disease.
U.S. Patent Application No. 20020052374 (Rabelink, et al., 2002) describes the use of at least folic acid or a folate and tetrahydrobiopterin (BH4) or derivatives thereof for treating or preventing cardiovascular or neurological disorders by modulation of the activity of nitric oxide synthase (NOS) in the form of a pharmaceutical preparation suitable for influencing the nitric oxide (NO) level, particularly by modulation of the activity of nitric oxide synthase (NOS) by reducing superoxide (O2) production and enhancing nitric oxide (NO) synthesis.
WIPO Publication Nos. 2008075959 & 2008075957 (Aerts, 2008) discloses a pathogenic factor allowing diagnosis of Fabry disease. In particular lyso-ceramide trihexosamide (lyso-CTH) has been found to function as a diagnostic marker for Fabry disease and an improved therapy for Fabry disease based on the identification of the pathogenic factor in the plasma.
United States Patent Application No. 20050197341 (Woolf et al., 2005) teaches a method of treating, reducing, or preventing pain and/or the consequences or development of a peripheral nerve lesion in a mammal by administering a composition that reduces the tetrahydrobiopterin (BH4) biological activity in an amount sufficient to treat, reduce, or prevent pain or the exacerbation of a peripheral nerve lesion due to overproduction of BH4.
U.S. Pat. No. 4,774,244 (Curtius et al., 1988) teaches the use of L-erythro-5,6,7,8-tetrahydrobiopterin, L-sepiapterin, 1′,2′-diacetyl-5,6,7,8-tetrahydrobiopterin and 6-methyl-5,6,7,8-tetrahydropterin can be used for the therapeutic treatment of patients with Parkinson's disease and of patients with depression.